Processes for the preparation of oral dosage formulations of modafinil

ABSTRACT

The invention relates to processes for preparing, and pharmaceutical compositions of, modafinil dosage forms for oral administration. The dosage forms include a mixture of coarse and fine particles of modafinil. The process for preparing modafinil oral dosage forms includes forming a dosage form that includes about 7%-25% by weight of modafinil particles having diameters greater than 220 μm and about 75%-93% by weight of modafinil particles having diameters less than 220 μm.

FIELD OF THE INVENTION

[0001] The technical field of the invention relates to processes forpreparing, and pharmaceutical compositions of, modafinil dosage formsfor oral administration. The dosage forms include a mixture of coarseand fine particles of modafinil.

BACKGROUND OF THE INVENTION

[0002] Modafinil is a wakefulness-promoting agent indicated for use innarcolepsy and idiopathic hypersomnia. It also is used for improvingmemory and mood. Compared to amphetamines and methylphenidate, modafinilis less likely to cause jitteriness, anxiety, or excess locomotoractivity. The precise mechanism of action is not fully understood but itis thought to modulate the central postsynaptic alpha₁-adrenergicreceptors. However, modafinil has a different pharmacokinetic profilecompared to the sympathomimetic agents, such as amphetamines andmethylphenidate.

[0003] The benzhydrylsulfinyl acetamide structure of modafinil makes itinsoluble in water (less than 1 mg/ml) as well as unstable at highertemperatures. These physicochemical properties decrease the drug'spotential for abuse via injection or smoking, and lead to reduced casesof dependency compared to amphetamines.

[0004] Over the years, more than 40% of the potential candidates in drugdiscovery and research have failed to emerge as drugs due to their poorbiopharmaceutic properties. Most of these are rejected due to poorsolubility characteristics and further development is continued only ifthe new molecule has some marked advantage over the existing moleculesindicated for the similar use.

[0005] The most common approach used to address the problem ofinsolubility is by either reducing the drug's particle size ormicronizing the drug to the size of a few microns, which increases theeffective exposed surface area. Dosage forms which contain micronizeddrug particles exhibit enhanced solubility and consequently an increasein the bioavailability of the drugs. However, technical and economicalproblems can arise. For example, highly micronized drug particlespossess poor flow properties and an increased chance of re-agglomerationduring processing. In some cases, re-agglomeration of micronized drugparticles may be so problematic that the basic objective of enhancingthe solubility by increasing the effective surface area may be unmet.

[0006] U.S. Pat. No. RE 37,516 discloses a method of size reduction anda pharmaceutical composition that has at least 95% of the modafinilparticles having a diameter of less than 200 μm.

SUMMARY OF THE INVENTION

[0007] In one general aspect, there is provided a pharmaceuticalcomposition of modafinil that includes a combination of coarse and fineparticles of modafinil.

[0008] In another general aspect there is provided a process forpreparing an oral dosage form containing modafinil. The process includesforming a dosage form that includes about 7%-25% by weight of modafinilparticles have diameters greater than 220 μm and about 93%-75% by weightof modafinil particles have diameters less than 220 μm.

[0009] Embodiments of the process of forming the oral dosage form mayinclude one or more of the following features. For example, forming adosage form may further include mixing the modafinil particles ingeometric progression with one or more pharmaceutically acceptableexcipients to form a blend. Forming a dosage form may still furtherinclude granulating the blend to form granules, optionally drying thegranules, sizing the granules, mixing the sized granules with one ormore extragranular pharmaceutically acceptable excipients, andcompressing into a tablet.

[0010] Forming the dosage form may further include blending themodafinil particles with one or more pharmaceutically inert excipientsto form a blend, granulating the blend to form granules, blending thegranules with one or more pharmaceutically inert excipients, andcompressing or filling into a solid dosage form. Granulating may be wetgranulation or dry granulation. The dosage form may be a tablet and theprocess may further include coating the tablet.

[0011] Forming the dosage form also may further include blending themodafinil particles with one or more pharmaceutically inert excipientsto form a blend and compressing the blend or filling the blend into asolid dosage form.

[0012] Of the dosage form, about 7% by weight of the modafinil particlesmay have diameters greater than 220 μm and about 93% by weight of themodafinil particles may have diameters less than 220 μm. About 10% byweight of the modafinil particles may have diameters greater than 220 μmand about 90% by weight of the modafinil particles may have diametersless than 220 μm. About 15% by weight of the modafinil particles mayhave diameters greater than 220 μm and about 85% by weight of themodafinil particles may have diameters less than 220 μm. The specificsurface area of the modafinil particles may be at least 0.2 m²/gm. Thedosage form may release at least 75% of the modafinil in about 45minutes.

[0013] The oral dosage form may be a tablet or a capsule and the tabletis formed by either wet granulation, dry granulation, or directcompression. The process may further include coating the tablet.

[0014] The dosage form may include one or more pharmaceuticallyacceptable excipients. The pharmaceutically acceptable excipients may beone or more of binders, diluents, disintegrants, surfactants,lubricants, glidants, and coloring agents.

[0015] In another general aspect, there is provided an oral dosage formof modafinil including about 7% to 25% by weight of modafinil particleshaving diameters greater than 220 μm and about 93% to 75% by weight ofmodafinil particles having diameters less than 220 μm. The dosage formreleases at least 75% of the modafinil in about 45 minutes.

[0016] Embodiments of the dosage form may include one or more of thefollowing features. For example, about 7% by weight of the modafinilparticles may have diameters greater than 220 μm and about 93% by weightof the modafinil particles may have diameters less than 220 μm. About10% by weight of the modafinil particles may have diameters greater than220 μm and about 90% by weight of the modafinil particles may havediameters less than 220 μm. About 15% by weight of the modafinilparticles may have diameters greater than 220 μm and about 85% by weightof the modafinil particles may have diameters less than 220 μm. Thespecific surface area of the modafinil particles may be at least 0.2m²/gm.

[0017] The oral dosage form may be a tablet or capsule. The oral dosageform may further include one or more pharmaceutically acceptableexcipients. The pharmaceutically acceptable excipients may be one ormore of binders, diluents, disintegrants, surfactants, lubricants,glidants, and coloring agents.

[0018] In another general aspect, there is provided a method of treatinga condition using modafinil. The method of treating includes providingan oral dosage form of modafinil that includes about 7% to 25% by weightof modafinil particles have diameters greater than 220 μm and about 93%to 75% by weight of modafinil particles have diameters less than 220 μm.The dosage form releases at least 75% of the modafinil in about 45minutes.

[0019] Embodiments of the method of treating with modafinil may includeone or more of the following features. For example, the condition may beone or both of narcolepsy and idiopathic hypersomnia.

[0020] Of the dosage form, about 7% by weight of the modafinil particlesmay have diameters greater than 220 μm and about 93% by weight of themodafinil particles may have diameters less than 220 μm. About 10% byweight of the modafinil particles may have diameters greater than 220 μmand about 90% by weight of the modafinil particles may have diametersless than 220 μm. About 15% by weight of the modafinil particles mayhave diameters greater than 220 μm and about 85% by weight of themodafinil particles may have diameters less than 220 μm. The specificsurface area of the modafinil particles may be at least 0.2 m 2/gm.

[0021] The oral dosage form used to treat the condition may be a tabletor capsule. The oral dosage form may further include one or morepharmaceutically acceptable excipients. The pharmaceutically acceptableexcipients may be one or more of binders, diluents, disintegrants,surfactants, lubricants, glidants, and coloring agents.

[0022] In another general aspect, there is provided an oral dosage formthat includes an intragranular portion and an extragranular portion. Theintragranular portion includes about 7% to 25% by weight of modafinilparticles having diameters greater than 220 μm, about 93% to 75% byweight of modafinil particles having diameters less than 220 μm, and oneor more pharmaceutically acceptable excipients. The extragranularportion includes one or more pharmaceutically acceptable excipients.

[0023] Embodiments of the oral dosage form may include one or more ofthe following features. For example, the oral dosage form may releaseone or more of between 48% and 81% of the modafinil within 15 minutes,between 68% and 87% of the modafinil within 30 minutes, between 76% and95% of the modafinil within 45 minutes, between 84% and 97% of themodafinil within 60 minutes, and between 89% and 98% of the modafinilwithin 90 minutes. The modafinil is released in a USP Apparatus II, in900 ml of water, and stirred at 50 rpm. The oral dosage form may beprovided with labeling for one or more of wakefulness promotion, toimprove wakefulness in patients with excessive daytime sleepinessassociated with narcolepsy, and idiopathic hypersomnia.

[0024] The details of one or more embodiments of the inventions are setforth in the description below. Other features, objects, and advantagesof the invention will apparent from the description and the claims.

DETAILED DESCRIPTION OF THE INVENTION

[0025] The inventors have recognized that there is an unmet need for asimple, cheaper, and faster process of preparing modafinil dosage formshaving an improved dissolution rate without the processing problems ofthe prior art. In particular, the inventors have now discovered that theproblem of reagglomeration of micronized modafinil particles can beavoided by mixing coarse particles (diameters greater than 220 μm) andfine particles (diameters less than 220 μm) in a ratio of between about7:93 to about 25:75 by weight. The combination of coarse and fineparticles of the drug improves the flow properties of the compositionand thereby facilitates the processing of the dosage form with reducedproblems of reagglomeration. Further, the use of a combination of coarseand fine particles reduces the problem of drug loss and improves thehomogeneity of the drug particles. The present process also provides adosage form with almost total drug release within 60 to 90 minutes.

[0026] Recognizing the above problems, the inventors have developedprocesses for preparing modafinil oral dosage forms in which about 7% to25% by weight of the modafinil particles have diameters greater than 220μm and about 75% to 93% by weight of the modafinil particles havediameters less than 220 μm. Additionally, the dosage form made by theseprocesses release at least 75% of the drug in about 45 minutes.

[0027] As used herein the term “coarse” means modafinil particles havingdiameters greater than 220 μm and the term “fine” means modafinilparticles having diameters less than 220 μm. A particularly suitablemean particle size of fines is that of diameters less than 180 μm. Aneven more suitable mean particle size of fines is that of diameters lessthan 60 μm. The ratio of coarse and fine particles may vary from about7:93 to 25:75 by weight. Variations within this range generally do notaffect the dissolution profile of this modafinil dosage form.Preferably, the specific surface area of the combined coarse and finemodafinil particles is at least 0.2 m²/gm. The particle sizes aredetermined using, for example, a Malvern Master Sizer or by sieveanalysis.

[0028] The term ‘pharmaceutical composition’ as used herein includessolid dosage forms such as tablet, capsule, pill and the like. Thesedosage forms may be prepared by processes known in the art including,for example, comminuting, mixing, granulating, melting, sizing, filling,drying, molding, immersing, coating, compressing, etc.

[0029] The desired modafinil particle size may be obtained byconventional methods, such as milling and sieving. Methods ofcomminuting the modafinil particles may include air jet milling,multi-milling, ball milling or any other method of particle reduction.

[0030] In one of the embodiments, the pharmaceutical composition ofmodafinil is prepared by a wet granulation process that includes thesteps of blending coarse and fine modafinil particles with one or moreintragranular pharmaceutically inert excipients to form a blend; wetgranulating the blend with a granulating fluid or solution/dispersion ofone or more pharmaceutically inert excipients in the granulating fluidto form granules; drying and sizing the granules; optionally blendingthe dried and sized granules with one or more pharmaceutically inertextragranular excipients; and compressing that blend into tablets orfilling that blend into capsules. The pharmaceutical composition mayoptionally be coated with or more functional and/or non-functionalcoatings.

[0031] In another embodiment, the pharmaceutical composition ofmodafinil is prepared by a dry granulation process that includes thesteps of blending coarse and fine modafinil particles with one or moreintragranular pharmaceutically inert excipients to form a blend; drygranulating the blend by roller compactor or slugging to form granules;sizing the granules; optionally blending the sized granules with one ormore pharmaceutically inert extragranular excipients to form a blend;and compressing that blend into tablets or filling that blend intocapsules. The pharmaceutical composition may optionally be coated withor more functional and/or non-functional coatings.

[0032] In yet another embodiment, the pharmaceutical composition ofmodafinil is prepared by a direct compression process that includes thesteps of blending coarse and fine modafinil particles with one or morepharmaceutically inert excipients to form a blend and then compressingthe blend into tablets or filling the blend into capsules. Thepharmaceutical composition may optionally be coated with or morefunctional and/or non-functional coatings.

[0033] The pharmaceutical composition also may be prepared by mixing thecoarse and the fine modafinil particles in geometric progression withfiller(s) and disintegrant(s); wet granulating the blend with an aqueoussolution of binder; drying and sizing the granules; and compressing thegranules into a tablet.

[0034] Mixing solid ingredients in a geometric progression generallyrefers to a process of adding almost equal amounts of two ingredientsand then mixing to form a homogenous mixture of the two. This process isrepeated by further mixing equal amounts to the mixture until the entirefirst ingredient is consumed. The entire mixture then is divided into,for example, four equal proportions and small amounts are taken fromeach portion and mixed thoroughly. This mixing is continued by addingfrom each portion until all the portions are completely used. Themixture then is further divided into two portions and the above processis repeated and ultimately the entire mixture is mixed randomly.

[0035] The term “pharmaceutically acceptable inert excipients” as usedherein includes all excipients used in the art of manufacturing soliddosage forms. Examples include binders, diluents, disintegrants,surfactants, lubricants/glidants, coloring agents, and the like.

[0036] Specific examples of suitable binders include sugars, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose,povidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol,pullulan, pregelatinized starch, agar, tragacanth, sodium alginate,propylene glycol, and the like.

[0037] Specific examples of suitable diluents include calcium carbonate,calcium phosphate-dibasic, calcium phosphate-tribasic, calcium sulfate,microcrystalline cellulose, powdered cellulose, dextrates, dextrins,dextrose excipients, fructose, kaolin, lactitol, lactose, mannitol,sorbitol, starch, starch pregelatinized, sucrose, sugar compressible,sugar confectioners, and the like.

[0038] Specific examples of suitable disintegrants includecroscarmellose sodium, crospovidone and sodium starch glycolate and thelike.

[0039] Specific examples of suitable surfactants include both non-ionicand ionic (cationic, anionic and zwitterionic) surfactants suitable foruse in pharmaceutical dosage forms. These include polyethoxylated fattyacids and their derivatives, for example, polyethylene glycol 400distearate, polyethylene glycol-20 dioleate, polyethylene glycol 4-150mono dilaurate, polyethylene glycol-20 glyceryl stearate; alcohol-oiltransesterification products, for example, polyethylene glycol-6 cornoil; polyglycerized fatty acids, for example, polyglyceryl-6pentaoleate; propylene glycol fatty acid esters, for example, propyleneglycol monocaprylate; mono and diglycerides, for example, glycerylricinoleate; sterol and sterol derivatives; sorbitan fatty acid estersand their derivatives, for example, polyethylene glycol-20 sorbitanmonooleate, sorbitan monolaurate; polyethylene glycol alkyl ether orphenols, for example, polyethylene glycol-20 cetyl ether, polyethyleneglycol-10-100 nonyl phenol; sugar esters, for example, sucrosemonopalmitate; polyoxyethylene-polyoxypropylene block copolymers knownas “poloxamer”; ionic surfactants, for example, sodium caproate, sodiumglycocholate, soy lecithin, sodium stearyl fumarate, propylene glycolalginate, octyl sulfosuccinate disodium, palmitoyl carnitine; and thelike.

[0040] Specific examples of suitable lubricants/glidants includecolloidal silicon dioxide, aerosol, stearic acid, magnesium stearate,magnesium silicate, hydrogenated vegetable oils, sodium stearylfumarate, calcium stearate, polyethylene glycol, sodium lauryl sulphate,sodium benzoate, talc, hydrogenated castor oil, sucrose esters of fattyacid, microcrystalline wax, yellow beeswax, white beeswax, and the like.

[0041] Coloring agents include any FDA colors approved for oral use.

[0042] Specific examples of suitable granulating fluids employed in theabove preparations of pharmaceutical compositions include methylenechloride, isopropyl alcohol, acetone, methanol, ethanol, water, and thelike.

[0043] The following examples further exemplify the invention and arenot intended to limit the scope of the invention. TABLE 1 Formulationdetails for Modafinil Tablets Example #1 Example #2 Example #3INGREDIENT (mg/tablet) (mg/tablet) (mg/tablet) Intragranular PortionModafinil (greater 30 30 20 than 220 μm) Modafinil (less than 170 (d₉₀41; 170 (d₉₀ 23; 180 (d₉₀ 23; d₅₀ 220 μm) d₅₀ 21)* d₅₀ 12)* 12)* Lactose132 132 132 Starch 125 125 125 Croscarmellose 10 10 10 Sodium Povidone10 10 10 Purified water q.s. q.s. q.s. Extragranular PortionCroscarmellose 10 10 10 sodium Colloidal silicon 5 5 5 dioxide Talc 5 55 Magnesium stearate 2.5 2.5 2.5

[0044] Procedure for producing tablets of modafinil:

[0045] 1. The modafinil particles were mixed in geometric progressionwith starch, lactose and intragranular croscarmellose sodium to form ablend.

[0046] 2. A water solution of povidone was prepared and used forgranulating the above blend to form granules.

[0047] 3. The granules were dried at 60° C.; sized; and mixed withextragranular croscarmellose sodium, colloidal silicon dioxide, talc,and magnesium stearate.

[0048] 4. The mixture of granules and extragranular ingredients thenwere compressed into tablets.

[0049] As described below, between 89% and 98% of the drug was releasedin 60-90 minutes at 50 rpm using dissolution test apparatus USP II andwater as the media wherein the drug has low solubility. The dissolutionprofiles of modafinil tablets prepared as per Examples 1-3 are given inTable 2. TABLE 2 Dissolution data using USP Apparatus II, 900 ml, 50rpm, water (values are indicated in cumulative percent release) TimeExample #1 (%) Example #2 (%) Example #3 (%) 15 min 81 75 48 30 min 8786 68 45 min 90 95 76 60 min 91 97 84 90 min 91 98 89

[0050] The dissolution data of Examples 1-3 demonstrates an ability andmethod to make a dosage form of modafinil in which the dissolution ofthe modafinil particles can be modified by varying the above ingredientsto select a desired dissolution profile in which a great majority of themodafinil particles are released within 60-90 minutes. For example, ifthere is a desire to provide a large initial release of the modafinil,e.g., within fifteen minutes, the formulations of Examples 1 and 2 aremost suitable. If there is a desire to provide less of an initialrelease of the modafinil, the formulation of Example 3 is most suitable.As can be seen from the data in Table 2, the dissolution profile can bemodified by varying the relative amounts of coarse and fine modafinilparticles, as well as by varying the size distribution of the fineparticles.

[0051] While several particular forms of the inventions have beendescribed, it will be apparent that various modifications andcombinations of the inventions detailed in the text can be made withoutdeparting from the spirit and scope of the inventions. For example, theoral dosage form of modafinil can be provided with labeling for one ormore of wakefulness promotion, to improve wakefulness in patients withexcessive daytime sleepiness associated with narcolepsy, and idiopathichypersomnia. Further, it is contemplated that any single feature or anycombination of optional features of the inventive variations describedherein may be specifically excluded from the claimed inventions and beso described as a negative limitation. Accordingly, it is not intendedthat the inventions be limited, except as by the appended claims.

We claim:
 1. A process for preparing an oral dosage form containingmodafinil, the process comprising: forming a dosage form comprisingabout 7%-25% by weight of modafinil particles have diameters greaterthan 220 μm; and about 75%-93% by weight of modafinil particles havediameters less than 220 μm.
 2. The process according to claim 1 whereinabout 7% by weight of the modafinil particles have diameters greaterthan 220 μm and about 93% by weight of the modafinil particles havediameters less than 220 μm.
 3. The process according to claim 1 whereinabout 10% by weight of the modafinil particles have diameters greaterthan 220 μm and about 90% by weight of the modafinil particles havediameters less than 220 μm.
 4. The process according to claim 1 whereinabout 15% by weight of the modafinil particles have diameters greaterthan 220 μm and about 85% by weight of the modafinil particles havediameters less than 220 μm.
 5. The process according to claim 1 whereinthe specific surface area of the modafinil particles is at least 0.2m²/gm.
 6. The process according to claim 1 wherein the dosage formreleases at least 75% of the modafinil in about 45 minutes.
 7. Theprocess according to claim 1 wherein the dosage form comprises a tabletor a capsule.
 8. The process according to claim 1 further comprising oneor more pharmaceutically acceptable excipients.
 9. The process accordingto claim 8 wherein the pharmaceutically acceptable excipients compriseone or more of binders, diluents, disintegrants, surfactants,lubricants, glidants, and coloring agents.
 10. The process according toclaim 1 wherein forming the dosage form comprises blending the modafinilparticles with one or more pharmaceutically inert excipients to form ablend, granulating the blend to form granules, blending the granuleswith one or more pharmaceutically inert excipients, and compressing orfilling into a solid dosage form.
 11. The process according to claim 10wherein granulating comprises wet granulation.
 12. The process accordingto claim 10 wherein granulating comprises dry granulation.
 13. Theprocess according to claim 10 wherein the dosage form comprises a tabletand the process further comprises coating the tablet.
 14. The processaccording to claim 1, wherein forming the dosage form comprises blendingthe modafinil particles with one or more pharmaceutically inertexcipients to form a blend and compressing the blend or filling theblend into a solid dosage form.
 15. The process according to claim 1wherein forming a dosage form further comprises mixing the modafinilparticles in geometric progression with one or more pharmaceuticallyacceptable excipients to form a blend.
 16. The process according toclaim 15 further comprising: granulating the blend to form granules;optionally drying the granules; sizing the granules; mixing the sizedgranules with one or more pharmaceutically acceptable excipients; andcompressing into a tablet.
 17. An oral dosage form of modafinilcomprising: about 7% to 25% by weight of modafinil particles havediameters greater than 220 μm; and about 93% to 75% by weight ofmodafinil particles have diameters less than 220 μm.
 18. The oral dosageform according to claim 17 wherein about 7% by weight of the modafinilparticles have diameters greater than 220 μm and about 93% by weight ofthe modafinil particles have diameters less than 220 μm.
 19. The oraldosage form according to claim 17 wherein about 10% by weight of themodafinil particles have diameters greater than 220 μm and about 90% byweight of the modafinil particles have diameters less than 220 μm. 20.The oral dosage form according to claim 17 wherein about 15% by weightof the modafinil particles have diameters greater than 220 μm and about85% by weight of the modafinil particles have diameters less than 220μm.
 21. The oral dosage form according to claim 17 wherein the specificsurface area of the modafinil particles is at least 0.2 m²/gm.
 22. Theoral dosage form according to claim 17 wherein the dosage form releasesat least 75% of the modafinil in about 45 minutes.
 23. The oral dosageform according to claim 17 wherein the dosage form comprises a tablet orcapsule.
 24. The oral dosage form according to claim 17 furthercomprising one or more pharmaceutically acceptable excipients.
 25. Theoral dosage form according to claim 24 wherein the pharmaceuticallyacceptable excipients comprises one or more of binders, diluents,disintegrants, surfactants, lubricants, glidants, and coloring agents.26. A method of treating a condition using modafinil, the method oftreating comprising: providing an oral dosage form of modafinilcomprising about 7% to 25% by weight of modafinil particles havediameters greater than 220 μm; and about 93% to 75% by weight ofmodafinil particles have diameters less than 220 μm.
 27. The methodaccording to claim 25 wherein about 7% by weight of the modafinilparticles have diameters greater than 220 μm and about 93% by weight ofthe modafinil particles have diameters less than 220 μm.
 28. The methodaccording to claim 25 wherein about 10% by weight of the modafinilparticles have diameters greater than 220 μm and about 90% by weight ofthe modafinil particles have diameters less than 220 μm.
 29. The methodaccording to claim 25 wherein about 15% by weight of the modafinilparticles have diameters greater than 220 μm and about 85% by weight ofthe modafinil particles have diameters less than 220 μm.
 30. The methodaccording to claim 25 wherein the specific surface area of the totalmodafinil particles is at least 0.2 m²/gm.
 31. The method according toclaim 25 wherein the dosage form releases at least 75% of the modafinilin about 45 minutes.
 32. The method according to claim 25 wherein thedosage form comprises a tablet or capsule.
 33. The method according toclaim 25 further comprising one or more pharmaceutically acceptableexcipients.
 34. The method according to claim 33 wherein thepharmaceutically acceptable excipients comprise one or more of binders,diluents, disintegrants, surfactants, lubricants, glidants, and coloringagents.
 35. The method according to claim 25 wherein the conditioncomprises one or more of narcolepsy and idiopathic hypersomnia.
 36. Anoral dosage form of modafinil comprising an intragranular portion and anextragranular portion: the intragranular portion comprising about 7% to25% by weight of modafinil particles having diameters greater than 220μm, about 93% to 75% by weight of modafinil particles having diametersless than 220 μm, and one or more pharmaceutically acceptableexcipients; and the extragranular portion comprising one or morepharmaceutically acceptable excipients.
 37. The oral dosage formaccording to claim 36 wherein the oral dosage form releases one or moreof between 48% and 81% of the modafinil within 15 minutes, between 68%and 87% of the modafinil within 30 minutes, between 76% and 95% of themodafinil within 45 minutes, between 84% and 97% of the modafinil within60 minutes, and between 89% and 98% of the modafinil within 90 minutes.38. The oral dosage form according to claim 37 wherein the modafinil isreleased in a USP Apparatus II, in 900 ml of water, and stirred at 50rpm.
 39. The oral dosage form according to claim 36 wherein the oraldosage form is provided with labeling for one or more of wakefulnesspromotion, to improve wakefulness in patients with excessive daytimesleepiness associated with narcolepsy, and idiopathic hypersomnia.